Matsatsantsa, who played with 10 men after Lance Davids was sent off, progressed 8-2 on aggregate thanks to their 3-0 win at home a fortnight ago.
Bongani Khumalo and Glen Salmon scored to make tie the scores going into half-time, and further goals from Brent Carelse, Daine Klate and Anthony Laffor ensured a comfortable win.
SuperSport will now meet Uganda’s KCC, who go went through 3-2 on aggregate against Ferroviario Maputo of Mozambique after a 2-0 win in the second leg.
Ajax Cape Town, who drew a bye in the first round, will meet Zimbabwe’s Monomatapa, who lost 2-1 to Zanzibar champions Miembeni, but progressed 3-2 on aggregate.
Kenyan club Mathare United lost 5-1 to visiting Zesco United of Zambia. Zesco now meet Ivoirians Africa Sports, who drew a bye in the first leg.
Defending champions Al-Ahly of Egypt, whose Final victory over Cotonsport of Cameroon last November gave them a record sixth title, are among 11 clubs who received byes.